engleski

Epigenetic modulation of N-glycome from HepG2 cells

Protein N-glycosylation is an important posttranslational modification which affects protein structure and function. A great amount of plasma proteins are synthesized in liver and changes in the plasma glycans are often associated with different types of liver diseases, including hepatocellular carcinoma (HCC). HepG2 cell line is a hepatocellular carcinoma cell line and its secretome is comparable with secretomes of HCC patients. Using different concentrations of DNA methylation inhibitors (5-aza- citidine, 5-aza-2-deoxycitidine and Zebularine) we have induced hypomethylation in HepG2 cells. Following 72h treatment with the inhibitors, HepG2 cell population was evaluated for survival, cell cycle stage, and karyotype changes, and glycans were measured from the HepG2 secretome using HILIC and MS. The treatment with all three epigenetic inhibitors resulted in changed DNA methylation and glyco-gene expression level, as well as in N-glycome composition of HepG2 secretome. The presented work contributes to our understanding of DNA methylation inhibitor efficiency in altering the N-glycan profiles of secreted proteins, but also shows the need for precise dosage of known epigenetic therapies.

DNA methylation ; N-glycosylation ; DNA methylation inhibitor ; HepG2

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